chr2-88691782-C-T

Variant names:

• chr2-88691782-C-T
• rs549384459
• NM_144563.3:c.84C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_144563.3(RPIA):​c.84C>T​(p.Gly28Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,592,612 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: RPIA NM_144563.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.12
• Publications: 0 publications found

Genes affected

RPIA (HGNC:10297): (ribose 5-phosphate isomerase A) The protein encoded by this gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway. This gene is highly conserved in most organisms. The enzyme plays an essential role in the carbohydrate metabolism. Mutations in this gene cause ribose 5-phosphate isomerase deficiency. A pseudogene is found on chromosome 18. [provided by RefSeq, Mar 2010]

RPIA Gene-Disease associations (from GenCC):

• ribose-5-P isomerase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 2-88691782-C-T is Benign according to our data. Variant chr2-88691782-C-T is described in ClinVar as Benign. ClinVar VariationId is 742902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00116 (176/152272) while in subpopulation AFR AF = 0.00409 (170/41562). AF 95% confidence interval is 0.00359. There are 1 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144563.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPIA	NM_144563.3	MANE Select	c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 9	NP_653164.2	P49247

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPIA	ENST00000283646.5	TSL:1 MANE Select	c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000283646.3	P49247
	RPIA	ENST00000871060.1		c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 9	ENSP00000541119.1
	RPIA	ENST00000871058.1		c.84C>T	p.Gly28Gly	synonymous	Exon 1 of 8	ENSP00000541117.1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 175 AN: 152154 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000315 AC: 64 AN: 203230 AF XY: 0.000249

Gnomad AFR exome AF: 0.00475

Gnomad AMR exome AF: 0.000227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 184 AN: 1440340 Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 77 AN XY: 715412

African (AFR) AF: 0.00455 AC: 151 AN: 33214

American (AMR) AF: 0.000309 AC: 13 AN: 42072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25714

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46104

Middle Eastern (MID) AF: 0.000661 AC: 3 AN: 4542

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105082

Other (OTH) AF: 0.000235 AC: 14 AN: 59530

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152272 Hom.: 1 Cov.: 33 AF XY: 0.00114 AC XY: 85 AN XY: 74460

African (AFR) AF: 0.00409 AC: 170 AN: 41562

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000854 Hom.: 0

Bravo AF: 0.00126

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.3
DANN	Benign	0.91
PhyloP100		-3.1
PromoterAI		-0.0040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs549384459; hg19: chr2-88991300;